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Air pollution is a global health threat and causes millions of human deaths annually. Outdoor and indoor air pollutants such as polycyclic aromatic hydrocarbons (PAHs) are the most prevalent cause of respiratory disorders, lung disease, pregnancy disorders, endocrine disturbances, diabetes, obesity, cardiovascular disease and cancer because pollutants can alter gene expression via epigenetics like DNA methylation and histone modifications which can initiate tumorigenesis and progressed to cancer. Carcinogenicity of PAHs can be eliminated by endogenous melatonin hormone (MT) via binding to its receptor (MTNR1A) that act as free radicals scavenger therefore it protects the body from developing occupational cancer. Aims of study To predict the protective effect of melatonin hormone as anti-cancer through binding to its receptor (MTNR1A) against any type of cancer that can be induced by chronic exposure to air pollutants. Subjects and methods This study includes 168 participants, they have been divided into three groups (control, refinery field workers and refinery office workers). PAH was analyzed for each participant by GC/MS whereas melatonin hormone and MTNR1A were measured by ELISA technique. Results PAHs were absent in the blood of control, and they were elevated in refinery worker’s specimens. Concentration of MT was higher in field worker than in office and control group as well as MTNR1A, also there is a relation between their levels and duration of exposure. Conclusion Exposure to PAHs can lead to oxidative stress that can damage DNA resulting in many types of cancer but this carcinogenic effects of PAHs can be eliminated by natural endogenous biomolecules such as MT and its receptor (MTNR1A) therefore their elevation has a beneficial effect as anti-cancer to reduce the oxidative stress and prevent tumorigenesis.

It has been revealed that benzo(a)pyrene is not only a background pollutant of the environment, but it is a highly toxic substance that easily enters the body of active and passive smokers through the respiratory tract. This substance is carcinogenic and causes intoxication, as well as various types of complex diseases. Degradation of benzo(a)pyrene in the environment occurs due to ultraviolet radiation, as well as exposure to photooxidants, primarily nitrogen oxides and ozone.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)–DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI–DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA–DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.

DNA is one of the most critical targets for many artificial agents listed as carcinogens. Most of them irreversibly bind to the DNA and induce genome mutation; therefore, it is vital to study the nature of binding of these molecules to anticipate their toxicity. The interaction between the textile dye reactive red 231 and salmon sperm double-stranded DNA (ss-dsDNA) was investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and ultraviolet-visible spectroscopy (UV–vis spectroscopy). Changes in the anodic current signals of the dye were observed in the presence and absence of ss-dsDNA at a glassy carbon electrode (GCE) using CV. The diffusion coefficient (D) was found to be 2.2 × 10–7 and 9.5 × 10–8 cm2 s−1 from the CV data for the free dye and dye-DNA complex, respectively. Electrochemical and UV–vis spectroscopy indicated 1:1 complex formation of the dye with DNA. The binding constant (kb) between the dye and DNA was calculated to be 5.4 × 105 M–1 and 4.9 × 105 M–1 at pH 4.0 using CV and UV–vis spectroscopy, respectively. Overall, these results suggest that the dye binds to DNA through the combined effect of intercalation and electrostatic interactions. DNA damage was also detected through changes in the voltammetric behaviour of the dye.

Background: Smokeless tobacco (SLT) is traditionally used in Middle East countries. The several toxic constituents with potential carcinogenicity make it a serious human health risk. Literature regarding their effects on cardiac and cancer disease is lacking in Saudi Arabia. Objective: This study was conducted to investigate the adverse effect of 11 different samples of widely used SLT varieties from the Tabuk region - Saudi Arabia, on Nitric Oxide (NO) level and their potential risk on cardiovascular health, etiology and/or progression of cancers. Methods: Samples were collected from Tabuk, KSA and analyzed by the GC-MS technique. Nitric oxide inhibition was performed using J774.2 macrophages by the Griess method. The retrieved crystallized structure of human inducible nitric oxide synthase (iNOS) from Brookhaven Protein Data Bank Repository PDB I.D: 3E7G with 2.20Å resolution was further prepared by structure using the MOE.2019 tool. The compounds abstracted from 11 different Shammah varieties were sketched by the MOE-Builder tool. Minimization for both receptor and compounds was performed via AMBER99 and MMFF99X force field implemented in MOE. Results: Nine samples (4 - 11) showed a potent suppressive effect on NO production with IC50 values ranging between (16.9-20.4 μg/mL), respectively. The samples (1 & 2) exhibited a moderate level of inhibition with IC50 ranging between 33.2 and 57.4 μg/mL, respectively. Interestingly, sample 4 consisting of compounds (13-15, 19-26, 28) that mostly belongs to the group fatty acid ester and phthalic acid ester showed the most potent suppressive effect. Molecular docking results revealed that the current local SLT constituents presented noticeable potency in different extract samples. Conclusion: Variable suppressive effects on NO were detected in the current SLT samples, where sample 4 was the most potent among all. The extract of the latter exhibited molecular interaction with the first shell amino acid residues of Inducible nitric oxide synthase (iNOS), which may anchor the plasticity and selectivity of the compounds present in it. The samples (4 -11) showed a potent inhibitory effect on the NO, where compound 26 (Phthalic acid ester) is common, and its adequate concentration may account for augmented biological activity. These results may effectively highlight their adverse effects on cardiovascular health and etiology and/or progression of cancer and may help in strengthening the social and governmental efforts in minimizing the use of these substances.

The conjugation of chitosan (CS) and folic acid (FA) was prepared and used to coat PLGA nanoparticles (NPs) that are loaded with Docetaxel (DTX) to target cancer cells that have lower pH and overexpression of folate receptors in comparison to normal cells. Three formulations had been prepared to reach the highest loading capacity (LC%) and encapsulation efficiency (EE%) and to study the effect of the amount of FA-CS on the drug release. The sizes, charges, homogeneity, surface morphology, LC% and EE% of the NPs were determined. The NPs were characterized using FTIR and XRD. In vitro release profiles of DTX from PLGA NPs, at pH 5.5 and 7.4 were determined. Finally, in vitro cytotoxicity assay on three cancer cell lines (RPMI 2650, Calu-3, and A549) was studied. The sizes of the three formulations ranged between 250.3±1.7 and 356.3±17.7. All prepared formulations showed acceptable monodispersity with highly positive charges. The EE% was above 85% and the LC% ranged between 6-35%. The in vitro release of DTX show an inverse relation to the amounts of FA-CS used and the pH of the dissolution medium. Coated PLGA NPs showed a significant difference in RPMI 2650, Calu-3, and A549 cell viability in comparison to free DTX. The NPs components were safe and non-toxic to human cells. In conclusion, coating PLGA NPs with FA-CS may be used as a good carrier for chemotherapeutic agents that selectively target carcinogenic tissues.

Arsenic is available in environment due to anthropogenic and natural activities. Arsenic trioxide is considered as neurotoxic, hepatotoxic, nephrotoxic, hemtoxic and carcinogenic. In present study Arsenic trioxide (As2O3) has been used as test chemical to evaluate its toxic potential in vital organs like brain, liver and kidney of male albino rat. 61 mature male Albino rats were used in present study. 36 were used for control, acute and sub-acute groups excluding 25 rats for the calculation of median lethal dose. Control group was unexposed to Arsenic trioxide whereas acute group includes 3 hrs, 6 hrs, 12 hrs and 1 day duration of exposure to As2O3. Likewise sub-acute group includes 7, 14, & 21 days treatment to Arsenic trioxide. Rats of acute and sub-acute groups were supplemented with As2O3 orally in mg/Kg body weight accordingly. Accumulation of Arsenic trioxide was higher in liver followed by kidney and brain. The aim of study is to extrapolate existing findings of retention potential of arsenic in vital organs and peripheral blood and consequently helpful in assessing the toxicity and hazardous effects of test chemical.

Background: Colorectal cancer (CRC) is increasing in low- and middle-income countries, likely due to changing lifestyle habits, including diet. We aimed to investigate the relationship between dietary betaine, choline, and choline-containing compounds and CRC risk. Methods: We analyzed data from a case–control study, including 865 CRC cases and 3206 controls from Iran. Detailed information was collected by trained interviewers using validated questionnaires. The intake of free choline, phosphocholine (Pcho), glycerophosphocholine (GPC), phosphatidylcholine (PtdCho), and sphingomyelin (SM), as well as of betaine was estimated from food frequency questionnaires and categorized into quartiles. The odds ratios (OR) and 95% confidence intervals (CI) of CRC for choline and betaine quartiles were calculated using multivariate logistic regression by adjusting for potential confounders. Results: We observed excess risk of CRC in the highest versus lowest intake of total choline (OR = 1.23, 95% CI 1.13, 1.33), GPC (OR = 1.13, 95% CI 1.00, 1.27), and SM (OR = 1.14, 95% CI 1.01, 1.28). The intake of betaine exerted an inverse association with CRC risk (OR = 0.91, 95% CI 0.83, 0.99). There was no association between free choline, Pcho, PtdCho, and CRC. Analyses stratified by gender showed an elevated OR of CRC in men for SM intake OR = 1.20, 95% CI 1.03, 1.40) and a significantly decreased CRC risk in women for betaine intake (OR = 0.84, 95% CI 0.73, 0.97). Conclusion: Dietary modifications leading to an increase in betaine sources and managing the use of animal products as references for SM or other choline types might contribute to decreasing the risk of CRC. publishedVersion

Peer reviewed: True, Funder: King’s College London, Funder: National Institute for Health Research (NIHR), Organoids are 3D cultures that to some extent reproduce the structure, composition and function of the mammalian tissues from which they derive, thereby creating in vitro systems with more in vivo-like characteristics than 2D monocultures. Here, the ability of human organoids derived from normal gastric, pancreas, liver, colon and kidney tissues to metabolise the environmental carcinogen benzo[a]pyrene (BaP) was investigated. While organoids from the different tissues showed varied cytotoxic responses to BaP, with gastric and colon organoids being the most susceptible, the xenobiotic-metabolising enzyme (XME) genes, CYP1A1 and NQO1, were highly upregulated in all organoid types, with kidney organoids having the highest levels. Furthermore, the presence of two key metabolites, BaP-t-7,8-dihydrodiol and BaP-tetrol-l-1, was detected in all organoid types, confirming their ability to metabolise BaP. BaP bioactivation was confirmed both by the activation of the DNA damage response pathway (induction of p-p53, pCHK2, p21 and γ-H2AX) and by DNA adduct formation. Overall, pancreatic and undifferentiated liver organoids formed the highest levels of DNA adducts. Colon organoids had the lowest responses in DNA adduct and metabolite formation, as well as XME expression. Additionally, high-throughput RT-qPCR explored differences in gene expression between organoid types after BaP treatment. The results demonstrate the potential usefulness of organoids for studying environmental carcinogenesis and genetic toxicology.

Arsenic and arsenic-containing compounds are considered human carcinogens. Both natural sources and anthropogenic activities such as mining, pesticide, glass and microelectronics manufacturing, and pharmaceuticals constitute the sources of environmental and/or occupational exposures. Cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, anemia, leukopenia and eosinophilia, and various types of cancer have all been associated with human exposure to arsenic. Research has also pointed out significantly higher standardized mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution. Both acute and chronic exposures have been reported in several countries where drinking water is contaminated with high concentrations of arsenic. Recent epidemiologic studies have demonstrated a strong correlation between arsenic exposure and the increased cancer incidence in humans. This chapter discusses the toxicological properties and the potential mechanisms of arsenic-induced toxicity, with a special emphasis on arsenic-induced carcinogenesis.

The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed through food, water, air, and soil. It causes various biological effects on cells and tissues. The metabolism of arsenic has an important role in its toxicity. This metabolism involves methyltransferase mediated reduction to a trivalent state followed by oxidative methylation to a pentavalent state. The pentavalent arsenicals are reported to be less potent toxicants than the trivalent arsenicals including those that are methylated. Arsenic-induced toxicity is believed to be mediated via reactive oxygen species (ROS) generation, Ca2+ accumulation, caspase-3 up-regulation, Bcl-2 down-regulation, and p-53 deficiency. Alterations of these factors from normal physiology might play prominent roles in carcinogenicity, cardiovascular, testicular, genotoxicity, diabetes, and nervous systems disorders. The exact mechanisms in arsenic toxicity and its subsequent organ pathophysiology are not well defined to date. Potential mechanisms of various types of arsenic-induced cancer may include oxidative stress, co-carcinogenesis and tumor promotion, genotoxicity, altered DNA methylation, altered cell proliferation, etc. As a preventive and curative measure of arsenic toxicity, combination therapies using antioxidants (N-acetylcysteine, α-lipoic acid, quercetin, etc.) and a thiol-chelating agent (with a proper chelator) can be considered as a better therapeutic approach than chelation therapy alone. We intend to summarize the up-to-date knowledge from literature on the molecular and cellular mechanisms of arsenic toxicity and usefulness of antioxidants in preventing these alterations.

Carcinogenicity testing in experimental animals is typically done under conditions that maximize the potential for detecting an effect. The scientific ideal is to evaluate a chemical’s carcinogenic potential from human data. While controlled exposure studies for carcinogenesis are not ethical, information can sometimes be obtained from epidemiology studies, particularly occupational studies involving high exposures to a limited number of chemicals. Carcinogenicity studies are the longest and most expensive of the extensive battery of toxicology studies required for the registration of pharmaceutical products in the United States, and in other major countries. Carcinogenicity bioassays have two primary objectives, though the second is now more important and (as our understanding of carcinogenesis has increased) is increasingly crowding out the first. The first objective is to detect possible carcinogens. The second objective for a bioassay is to provide a range of dose–response information (with tumor incidence being the response) so that a risk assessment may be performed.

Over the past few decades, the number of cancer cases attributed to environmental and occupational carcinogens, such as asbestos, arsenic, and indoor and outdoor air pollution, decreased in high-income countries. These exposures are expected to increase for low- to middle-income countries, where industrialization expands, and populations grow. Still, there are a small number of studies from these countries on carcinogenic occupational and environmental exposures and their associations with neoplastic outcomes. The estimation of human cancer's burden attributed to environmental and occupational exposures in low- to middle-income countries is uncertain. Despite the high incidence of carcinogenic exposures reported in many such countries, the exposures' effects are poorly studied due to different limitations, such as lack of resources and government support. It is highly relevant to review key exposures and outcomes related to specific environmental and occupational carcinogens in the context of global health challenges faced by developing countries, especially considering new findings on this topic in the last few years. © 2023 Nova Science Publishers, Inc. All rights reserved.

Aspergillus flavus (A. flavus) is one of the most important model environmental fungi which can produce a potent toxin and carcinogen known as aflatoxin. Aflatoxin contamination causes massive agricultural economic loss and a critical human health issue each year. Although a functional vacuole has been highlighted for its fundamental importance in fungal virulence, the molecular mechanisms of the vacuole in regulating the virulence of A. flavus remain largely unknown. Here, we identified a novel vacuole-related protein in A. flavus, the ortholog of phosphatidylinositol-3-phosphate-5-kinase (Fab1) in Saccharomyces cerevisiae. This kinase was located at the vacuolar membrane, and loss of fab1 function was found to affect the growth, conidia and sclerotial development, cellular acidification and metal ion homeostasis, aflatoxin production and pathogenicity of A. flavus. Further functional analysis revealed that Fab1 was required to maintain the vacuole size and cell morphology. Additional quantitative proteomic analysis suggested that Fab1 was likely to play an important role in maintaining vacuolar/cellular homeostasis, with vacuolar dysregulation upon fab1 deletion leading to impaired aflatoxin synthesis in this fungus. Together, these results provide insight into the molecular mechanisms by which this pathogen produces aflatoxin and mediates its pathogenicity, and may facilitate dissection of the vacuole-mediated regulatory network in A. flavus.

We have shown previously that exposing bacteria to tetrachlorocatechol (TCC) and sodium azide (NaN3) together causes synergistic cytotoxicity in a biphasic mode. However, the underlying chemical mechanism remains unclear. In this study, an unexpected ring-contraction 3(2H)-furanone and two quinoid-compounds were identified as the major and minor reaction products, respectively; and two unusual azido-substituted chloro-O-semiquinone radicals were detected and characterized as the major radical intermediates by complementary applications of direct ESR, HPLC/ESI-Q-TOF and high-resolution MS studies with nitrogen-15 isotope-labeled NaN3. Taken together, we proposed a novel molecular mechanism for the reaction of TCC/NaN3: N3- may attack on tetrachloro-O-semiquinone radical, forming two transient 4-azido-3,5,6-trichloro- and 4,5-diazido-3,6-dichloro-O-semiquinone radicals, consecutively. The second-radical intermediate may either undergo an unusual zwitt-azido cleavage to form the less-toxic ring-contraction 3(2H)-furanone product, or further oxidize to form the more toxic quinoid-product 4-amino-5-azido-3,6-dichloro-O-benzoquinone. A good correlation was observed between the biphasic formation of this toxic quinone due to the two competing decomposition pathways of the radical intermediate and the biphasic synergism between TCC and NaN3, which are dependent on their molar-ratios. This is the first report of detection and identification of two unique azido-substituted chloro-O-semiquinone radicals, and an unprecedented ring-contraction mechanism via an unusually mild and facile zwitt-azido rearrangement.

Background In a previous study, we estimated exposure prevalence and the number of workers exposed to carcinogens by industry in Korea. The present study aimed to evaluate the optimal exposure intensity indicators of airborne lead exposure by comparing to blood lead measurements for the future development of the carcinogen exposure intensity database. Methods Data concerning airborne lead measurements and blood lead levels were collected from nationwide occupational exposure databases, compiled between 2015 and 2016. Summary statistics, including the arithmetic mean (AM), geometric mean (GM), and 95th percentile level (X95) were calculated by industry both for airborne lead and blood lead measurements. Since many measurements were below the limits of detection (LODs), the simple replacement with half of the LOD and maximum likelihood estimation (MLE) methods were used for statistical analysis. For examining the optimal exposure indicator of airborne lead exposure, blood lead levels were used as reference data for subsequent rank correlation analyses. Results A total of 19,637 airborne lead measurements and 32,848 blood lead measurements were used. In general, simple replacement showed a higher correlation than MLE. The results showed that AM and X95 using simple replacement could be used as optimal exposure intensity indicators, while X95 showed better correlations than AM in industries with 20 or more measurements. Conclusion Our results showed that AM or X95 could be potential candidates for exposure intensity indicators in the Korean carcinogen exposure database. Especially, X95 is an optimal indicator where there are enough measurements to compute X95 values.

The survival of organisms is threatened with a variety of pollutants and chemical compounds and population growth. Natural phenomena and human activities, especially industrial activities increase contamination of water, soil and air. Population growth leads to increased exploitation of the sea and oceans, thus the consumption of seafood increases. In addition, the main food of the people in some areas is fish. Consumption of fish has numerous benefits to healthy for humans, but the existence of some heavy metals including lead, cadmium, and etc. may cause toxicity to marine organisms. The degree of heavy metal toxicity depends on their chemical form of metals. Some forms of metals are rapidly excreted and do not have the opportunity to be absorbed and stored in body tissues, accordingly they are not very toxic, while some forms of metals are highly toxic and lethal. These forms are slowly excreted from metals and have the ability to be absorbed and accumulated in fish muscles and other organs. Heavy metals cause harmful effects such as carcinogenesis, malformations, damage to the nervous system, damage to the reproductive system and infertility in men, liver failure and cardiovascular disease and so on. Therefore, in this review focused on concentration of heavy metals in fish muscle is essential to ensure the safety of this type of food.

Cigarette smoking is an established risk factor for oral cancer. The health effects of e-cigarettes are still under investigation but may disturb oral cavity homeostasis and cause lung and cardiovascular diseases. Carcinogens and toxicants in tobacco products and e-cigarettes may damage DNA, resulting in the formation of apurinic/apyrimidinic (AP) sites, and initiation of the carcinogenic process. In this study, we optimized a liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry method to analyze AP sites in buccal cell DNA of 35 nonsmokers, 30 smokers, and 30 e-cigarette users. AP sites in e-cigarette users (median 3.3 per 10(7) nts) were significantly lower than in smokers (median 5.7 per 10(7) nts) and nonsmokers (median 6.0 per 10(7) nts). AP sites in smokers were not significantly different from nonsmokers (p > 0.05). The e-cigarette vaporizing solvents propylene glycol and glycerin were tested and did not protect against AP site formation in in vitro control and carcinogen exposed rat liver homogenates. However, propylene glycol may inhibit bacteria in oral cells, resulting in reduced inflammation and related effects, and reduced AP site levels in e-cigarette user DNA. This is the first study to examine AP site formation in e-cigarette users and to evaluate AP sites in human oral cell DNA.

Baclofen is a γ-aminobutyric acid-B receptor agonist used for control of spastic muscle activity and as a treatment for alcohol abuse. The review of the nonclinical database suggested a data gap for potential carcinogenicity following long-term use. Regulatory requirements for pharmaceutical safety testing of cancer-causing potential have historically included 2-year rodent studies in rats and mice. The availability of transgenic models with greater specificity and sensitivity to carcinogens provides safety testing alternatives that align with the 3Rs. The carcinogenicity of baclofen was evaluated in CB6F1-TgrasH2 transgenic mice following daily oral administration at 45, 90, and 180 mg/kg/d for 26 weeks, preceded by a 2-week drug-conditioning period. There were no treatment-related palpable masses or neoplastic findings, and survival rates were not affected by the baclofen treatment. In conclusion, baclofen was considered as noncarcinogenic in CB6F1-TgrasH2 mice, which is consistent with results previously obtained in a 2-year rat study.

Medicinal plants (MPs) account for 70–80% of use in primary care around the world, and this percentage indicates that the number of MP users is high; thus, it is necessary to focus studies on medicinal herbs to ensure their proper use. In addition, MPs have strong genotoxic effects, as some types of MPs can cause DNA damage. Any substance that raises the risk of cancer or a tumor in an organism is called a carcinogen. There are many genotoxic and carcinogenic substances in the environment that can directly or indirectly affect genetic material. There are also nanoparticles (NPs) derived from MPs. Carbon-based NPs contain many nanoscale materials, such as fullerenes and carbon nanotubes, as well as metals such as gold (Au), silver (Ag), and aluminum (Al). Unfortunately, few studies are concerned with the carcinogenicity of NPs from MPs, whereas many researchers are interested in genotoxic assessment. For this reason, there is an urgent need for more studies into the safety of MPs and NPs. Therefore, this study reviewed the genotoxicity and carcinogenicity of MPs and their derived NPs. We also emphasized the need for strict regulation and monitoring of MP usage.

Introduction: Oral cytopathology is able to detect incipient cellular alterations, but it is not routinely applied to this purpose. We aimed to establish a model to screen individuals with no oral lesion exposed to smoking/alcohol, by means of the nuclear area, cell proliferation rate, and analysis of genetic damage. Methods: In this cross-sectional pilot study, 90 patients were allocated into 3 groups: oral cancer group (patients with oral squamous cell carcinoma), tobacco/alcohol group (patients without oral lesions and exposed to these risk factors), and control group (individuals with no lesion and not exposed to tobacco and alcohol). The cytological smears performed in these individuals were stained with Papanicolaou, a silver-staining and a Feulgen reaction. The nuclei of cells were measured, and AgNORs/nucleus and micronuclei (MN) were quantified. The cutoff values were stipulated evaluating the healthy mucosa (control group) and the cancerization field mucosa (oral cancer group). Results: Cutoff values for the screening of individuals exposed to carcinogens were ≥8% of nuclei larger than 100 μm2, ≥3.38 AgNOR/nucleus, and ≥3 MN per 1,000 cells. Conclusions: Nuclear area measurement and AgNORs/nucleus and MN quantification identified the incipient phase of oral carcinogenesis. A screening model for individuals without oral lesion exposed to smoking/alcohol was proposed.

Water samples at 13 sites were analyzed to evaluate heavy metals (cobalt, lead, manganese, copper) and benzo(a)pyrene using 2 methods of analysis (high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) kits). The Lesser Zap River is the main tributary of the Tigris and is used as a main source of drinking water in Kirkuk city through the General Kirkuk project. Risk evaluation for benzo(a)pyrene and lead in water samples was accomplished by Monte Carlo simulation. The highest concentrations of B(a)P were recorded at sites S7 and S5, with levels of 0.192 and 0.122 µg L−1 detected by HPLC and ELISA, respectively. The WHO guidelines for benzo[a]pyrene in drinking water recommend 0.7 µg L −1, and none of the samples surpassed this level; moreover, B(a)P levels exceeded EPA standards in 2014 (0.01 µg L−1), particularly when the liquid–liquid extraction method with HPLC was used. Carcinogenic risks for human adults and children exist and are highest during the rainy season as compared with the carcinogenic risk during the dry season and risks for children exceed those of adults. This indicates that the 2nd round of sampling (winter season) harbors more carcinogenic risk than the 1st round of sampling (dry season).

Chemicals are measured regularly in air, food, the environment, and the workplace. Biomonitoring of chemicals in biological fluids is a tool to determine the individual exposure. Blood protein adducts of xenobiotics are a marker of both exposure and the biologically effective dose. Urinary metabolites and blood metabolites are short term exposure markers. Stable hemoglobin adducts are exposure markers of up to 120 days. Blood protein adducts are formed with many xenobiotics at different sites of the blood proteins. Newer methods apply the techniques developed in the field of proteomics. Larger adducted peptides with 20 amino acids are used for quantitation. Unfortunately, at present the methods do not reach the limits of detection obtained with the methods looking at single amino acid adducts or at chemically cleaved adducts. Therefore, to progress in the field new approaches are needed. Supplementary Information The online version contains supplementary material available at 10.1007/s00204-021-03165-2.

Cadmium(II) is an omnipresent environmental toxicant emitted from various industrial sources and by anthropogenic sources such as smoking. Cadmium(II) enters our body through various sources including contaminated food and drinks and from active or passive smoking. It spares no organs in our body and the calamities it invites include primarily nephrotoxicity, osteotoxicity, teratogenicity, endocrine disruption, hepatotoxicity and carcinogenicity above all. It brings about a bolt from the blue in the cellular biochemistry by generating reactive oxygen species (ROS), disrupting the factors involved in the repair of DNA lesions and many other toxic nuisances otherwise by modulating the cell signalling machinery and acting as a potent carcinogen above all. In this review, we have tried to decipher some of the mechanisms played by cadmium(II) in exhibiting its toxic effects on various system of our body.

Aspergillus flavus is saprophytic soil fungus that contaminates seed crops with the carcinogenic secondary metabolite aflatoxin, posing a significant threat to humans and animals. Ferrous sulfate is a common iron supplement that is used to the treatment of iron-deficiency anemia. Here, we identified an unexpected inhibitory role of ferrous sulfate on A. flavus. With specific fluorescent dyes, we detected several conidial ferroptosis hallmarks in conidia under the treatment of 1 mM Fe2+, including nonapoptosis necrosis, iron-dependent, lipid peroxide accumulation, and ROS burst. However, unlike traditional ferroptosis in mammals, Fe2+ triggered conidial ferroptosis in A. flavus was regulated by NADPH oxidase (NOXs) activation instead of Fenton reaction. Transcriptomic and some other bioinformatics analyses showed that NoxA in A. flavus might be a potential target of Fe2+, and thus led to the occurrence of conidial ferroptosis. Furthermore, noxA deletion mutant was constructed, and both ROS generation and conidial ferroptosis in ΔnoxA was reduced when exposed to Fe2+. Taken together, our study revealed an exogenous Fe2+-triggered conidial ferroptosis pathway mediated by NoxA of A. flavus, which greatly contributes to the development of an alternative strategy to control this pathogen.

Environmental exposure of N-nitroso compounds (NOCs) from various sources like tobacco smoke, pesticides, smoked meat, and rubber manufacturing industries has been an alarming cause of carcinogenesis. Neonatal exposure to the carcinogenic N-N'ethylnitrosourea (ENU), a NOC has been established to cause leukemogenesis. Our world is constantly battling against cancer with consistent investigations of new anti-cancer therapeutics. Plant derived compounds have grasped worldwide attention of researchers for their promising anti-cancer potentials. Eclipta prostrata is one such ayurvedic herb, renowned for its anti-inflammatory properties. Currently, it has been explored in various cancer cell lines to establish its anti-cancer effect, but rarely in in-vivo cancer models. Wedelolactone (WDL), the major coumestan of E. prostrata is recognized as an inhibitor of IKK, a master regulator of the NF-kB inflammatory pathway. As persistent inflammation and activated inflammasome contribute to leukemogenesis, we tried to observe anti-leukemogenic efficacy of E. prostrata and its active compound WDL on the marrow cells of ENU induced experimental leukemic mice. Treatment groups were administered an oral gavage at a dose of 1200 mg/kg and 50 mg/kg b.w of crude extract and WDL respectively for 4 weeks. Various parameters like hemogram, survivability, cytological and histological investigations, migration assay, cell culture, flowcytometry and confocal microscopy were taken into consideration pre- and post-treatment. Interestingly, the plant concoction portrayed maximum effects in comparison to WDL alone. The study suggests E. prostrata and WDL as vital complementary adjuncts for anti-inflammasome mechanism in ENU-induced leukemia.

The mechanistic target of rapamycin complex 1 (mTORC1) acts as a central regulator of metabolic pathways that drive cellular growth. Abnormal activation of mTORC1 occurs at high frequency in human and mouse hepatocellular carcinoma (HCC). DEP domain-containing protein 5 (DEPDC5), a component of GATOR1 complex, is a repressor of amino acid-sensing branch of the mTORC1 pathway. In the current study, we found that persistent activation of hepatic mTORC1 signaling caused by Depdc5 ablation was sufficient to induce a pathological program of liver damage, inflammation and fibrosis that triggers spontaneous HCC development. Take advantage of the combinatory treatment with a single dose of diethylnitrosamine (DEN) and chronic feeding with high-fat diet (HFD), we demonstrated that hepatic depdc5 deletion did not aggravate DEN&HFD induced liver tumorigenesis, probably due to its protective effects on diet-induced liver steatosis. In addition, we further showed that chronic rapamycin treatment did not have any apparent tumor-suppressing effects on DEN&HFD treated control mice, whereas it dramatically reduced the tumor burden in mice with hepatic Depdc5 ablation. This study provides the novel in vivo evidence for Depdc5 deletion mediated mTORC1 hyperactivation in liver tumorigenesis caused by aging or DEN&HFD treatment. Moreover, our findings also propose that pharmacological inhibition of mTORC1 signaling maybe a promising strategy to treat HCC patients with mutations in DEPDC5 gene.

Arsenic is widely present in the environment and is associated with various population health risks including cancers. Arsenic exposure at environmentally relevant levels enhances the mutagenic effect of other carcinogens such as ultraviolet radiation. Investigation on the molecular mechanisms could inform the prevention and intervention strategies of arsenic carcinogenesis and co-carcinogenesis. Arsenic inhibition of DNA repair has been demonstrated to be an important mechanism, and certain DNA repair proteins have been identified to be extremely sensitive to arsenic exposure. This review will summarize the recent advances in understanding the mechanisms of arsenic carcinogenesis and co-carcinogenesis, including DNA damage induction and ROS generation, particularly how arsenic inhibits DNA repair through an integrated molecular mechanism which includes its interactions with sensitive zinc finger DNA repair proteins.

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants. They are constantly detected in terrestrial, ocean, and atmospheric systems, and it is of particular concern that these fat-soluble xenobiotics may have a negative impact on human health. This study aimed to evaluate the toxic effect and underlying mechanism of decabromodiphenyl ether (BDE-209) on human liver in a HepG2 cell model. The results showed that BDE-209 significantly induced HepG2 cells apoptosis, increased intracellular reactive oxygen species (ROS), disturbed [Ca 2+] homeostasis and mitochondrial membrane potential (MMP), and caused nuclear shrinkage and DNA double-strand breaks. BDE-209 also significantly decreased the activities of antioxidant parameters, superoxide dismutase (SOD), total antioxygenic capacity (T-AOC), glutathione (GSH), and total glutathione (T-GSH). The up-regulation of the Aryl hydrocarbon receptor (AhR)/cytochrome P4501A1 (CYP1A1) signaling pathway indicates that after long-term and high-dose exposure, BDE-209 may be a liver carcinogen. Interestingly, HepG2 cells attempt to metabolize BDE-209 through the Nrf2-mediated antioxidant pathway. These findings help elucidate the mechanisms of BDE-209-induced hepatotoxicity in humans.

Ubiquitin-conjugating enzyme E2S (UBE2S), an important E2 enzyme in the process of ubiquitination, has exhibited oncogenic activities in various malignant tumors. However, it remains unknown whether UBE2S plays a role in urinary bladder cancer (UBC) development. In the current study, our data confirmed UBE2S upregulation in UBC. In vitro and in vivo experiments demonstrated that UBE2S knockdown resulted in attenuated proliferation and enhanced apoptosis, which was inverse to the phenotypes with UBE2S overexpression. Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, we discovered that this UBE2S-modulated carcinogenic mechanism was in the consequence of directly targeting tuberous sclerosis 1 (TSC1), which is the upstream inhibitor of mTOR signaling for ubiquitous degradation. Taken together, this study demonstrated that UBE2S is a carcinogen in UBC and promotes UBC progression by ubiquitously degrading TSC1. This consequently mediates the activation of the mTOR pathway, suggesting a potential therapeutic regimen for UBC by targeting the newly identified UBE2S/TSC1/mTOR axis.

Humans are often exposed to mixtures of environmental pollutants especially environmental chemical carcinogens, representing a significant environmental health issue. However, our understanding on the carcinogenic effects and mechanisms of environmental carcinogen mixture exposures is limited and mostly relies on the findings from studying individual chemical carcinogens. Both arsenic and benzo(a)pyrene (BaP) are among the most common environmental carcinogens causing lung cancer and other types of cancer in humans. Millions of people are exposed to arsenic via consuming arsenic-contaminated drinking water and even more people are exposed to BaP via cigarette smoking and consuming BaP-contaminated food. Thus arsenic and BaP combined-exposure in humans is common. Previous epidemiology studies indicated that arsenic-exposed people who were cigarette smokers had significantly higher lung cancer risk than those who were non-smokers. Since BaP is one of the major carcinogens in cigarette smoke, it has been speculated that arsenic and BaP combined-exposure may play important roles in the increased lung cancer risk observed in arsenic-exposed cigarette smokers. In this review, we summarize important findings and inconsistencies about the co-carcinogenic effects and underlying mechanisms of arsenic and BaP combined-exposure and propose new areas for future studies. A clear understanding on the mechanism of co-carcinogenic effects of arsenic and BaP combined exposure may identify novel targets to more efficiently treat and prevent lung cancer resulting from arsenic and BaP combined-exposure.

Cervical cancer is the leading cause of morbidity and mortality in women throughout the world, human papillomavirus 16 (HPV16) is the main type of HPV causing invasive cervical cancer. However, the underlying mechanism of the high carcinogenicity of HPV16 remains unclear. In the current study, we documented that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA, is upregulated in HPV16-positive cervical cancer tissue and cell lines. The results of immunohistochemistry and immunofluorescence showed that MALAT1 was mainly localized in the cytoplasm. To clarify the biological functions of MALAT1 in cervical cancer cells, we performed gain- and loss-of-function experiments to explore the underlying molecular mechanism. Functionally, the proliferation of cervical cancer was detected by Cell Counting Kit-8 (CCK-8) and colony formation assay in MALAT1 overexpression or knockdown cells, our data showed that MALAT1 promotes the proliferation of cervical cancer cells. Mechanistically, our results suggested that MALAT1 upregulates Methionine adenosyltransferase 2A (MAT2A) by sponging miR-485-5p. Moreover, the gain-of-function assay validated the function of MAT2A in HPV16-positive cervical cancer proliferation. Taken together, our results demonstrated that MALAT1 acts as a competitive endogenous RNA (ceRNA) to regulate MAT2A by sponging miR-485-5p in HPV16-positive cervical cancer, suggesting that MALAT1 may act as a potential therapeutic target for HPV16-positive cervical cancer.

Marek's disease (MD), an immunosuppressive disease induced by Marek's disease virus (MDV), provides an ideal model for studying diseases caused by a carcinogenic virus. CD79B is a B-cell antigen receptor complex-associated protein β-chain precursor which is involved in the activation, proliferation, differentiation of B-cell and the transmission of downstream signals. This study analyzed CD79B gene mRNA expression and methylation by two schemes #20 (5´ flanking to intron 1) and #27 (intron 2 to intron 3), between MDV-infected tumorous spleens (TS) and non-infected spleens (NS). Results showed that average methylation levels of CpGs in #20 and #27 were higher in TS than in NS (P

The aim of the study was to analyze data on the exposure of military personnel to carcinogenic chemical substances, ionizing radiation and technological processes.Reports collected from the Military Centers of Preventive Medicine on carcinogens and exposure of workers in military units and institutions were subjected to a detailed analysis.The number of workers exposed to carcinogenic factors increased in the period under analysis. In 2019, the total number of people exposed in the workplace to chemical carcinogens or mutagens was 4058, to ionizing radiation - 1015, and to technological processes with carcinogenic or mutagenic effects - 12, compared to 3224, 1289 and 8 people, respectively, in 2018. The most common chemical agents in military units which caused exposure, from the point of view of occupational health and safety, were mixtures of liquid hydrocarbons used as fuel for driving vehicles and devices with internal combustion engines. In military units dedicated to the provision of medical services, exposure to X-ray radiation (diagnostics imaging) and formaldehyde (pathomorphology) was the most common.The collected data presents different approaches of individuals in terms of reporting and assessing occupational exposure. Understanding the long-term health effects requires more thorough research. Med Pr. 2021;72(5):501-8.Celem niniejszej pracy było przeprowadzenie analizy danych dotyczących narażenia pracowników jednostek wojskowych na substancje chemiczne, promieniowanie jonizujące i procesy technologiczne o działaniu kancerogennym.Szczegółowej analizie poddano raporty zebrane z Wojskowych Ośrodków Medycyny Prewencyjnej dotyczące czynników rakotwórczych oraz narażenia pracowników w jednostkach i instytucjach wojskowych.Liczba pracowników narażonych na działanie czynników o właściwościach kancerogennych w omawianym czasie wzrosła. W 2019 r. liczba osób narażonych w miejscu pracy na chemiczne substancje rakotwórcze lub mutagenne wynosiła 4058, promieniowanie jonizujące – 1015, procesy technologiczne o działaniu rakotwórczym lub mutagennym – 12, natomiast w roku 2018 – odpowiednio: 3224, 1289 i 8. W jednostkach wojskowych najbardziej rozpowszechnionymi czynnikami chemicznymi, na które występowało narażenie z punktu widzenia bezpieczeństwa i higieny pracy, były mieszaniny ciekłych węglowodorów stosowane jako paliwo do napędu pojazdów i urządzeń wyposażonych w silniki spalinowe. W jednostkach wojskowych ukierunkowanych na świadczenie usług medycznych najczęściej występowało narażenie na promieniowanie rentgenowskie (diagnostyka obrazowa) i formaldehyd (patomorfologia).Zebrane dane prezentują różne podejście jednostek w zakresie raportowania i oceny narażenia zawodowego. Poznanie długotrwałych skutków zdrowotnych wymaga przeprowadzenia dokładniejszych badań. Med. Pr. 2021;72(5):501–508.

Nowadays multiple heterogeneous chemicals affect the human body. They include drugs, household chemicals, dyes, food supplements and others. The human organism can modify, inactivate, and eliminate the chemicals by biotransformation enzymes. But it is well known that biotransformation can lead to toxification phenomenon. Individuals differ from each other by the rate of chemical modification that promotes accumulation of toxins and carcinogens in some patients. An N-acetyltransferase 2 enzyme participates in the aromatic amines second phase metabolism. This work reviews the acetyltransferase gene polymorphism possible role in diseases development including drug-induced organs damage.Gene of acetyltransferase has polymorphisms associated with two haplotypes of fast and slow substrate acetylation. Gene alleles combine in three genotypes: fast, intermediate, and slow acetylators. Acetylation rate plays a significant role in side effects development during tuberculosis treatment and cancer pathogenesis. Recently, new data described the role of enzyme in development of non-infectious diseases in the human. Scientists consider that slow acetylation genotype in combination with high xenobiotic load result in accumulation of toxic substances able to damage cells.Therefore, acetyltransferase genotyping helps to reveal risk groups of cancer and non-infectious disease development and to prescribe more effective and safe doses of drugs.

Colloidal Silver nano-particles were grown at room temperature using leaf extract of Ocimum tenuiflorum. The silver nanoparticles suspended in the solution were found to be stable for over a period of 2 months. Structural, optical and photo catalytic behavior of the suspended silver (Ag) nano-particles (NPs) was characterized. From TEM analysis the size of the silver nanoparticles was estimated to be 25–30 nm. Our findings suggest that the ratio between the molarity of AgNO3 and the volume of leaf extract does not have any role in controlling the size of the Ag nano-particles. These green synthesized Ag nano-particles exhibit degradation of the carcinogenic organic pollutant sulforhodamine B in absence of light.

Breast cancer is the leading cause of cancer-related death in women worldwide. Several studies have addressed the association between cancer in humans and agricultural pesticide exposure. Evidence indicates that exposure to organophosphorous pesticides such as parathion and malathion occurs as a result of occupational factors since they are extensively used to control insects. On the other hand, estrogens have been considered beneficial to the organism; however, epidemiological studies have pointed out an increased breast cancer risk in both humans and animals. Experimental female rat mammary gland cancer models were developed after exposure to parathion, malathion, eserine, an acetylcholinesterase inhibitor, and estrogen allowing the analysis of the signs of carcinogenicity as alteration of cell proliferation, receptor expression, genomic instability, and cell metabolism in vivo and in vitro. Thus, pesticides increased proliferative ducts followed by ductal carcinoma; and 17β-estradiol increased proliferative lobules followed by lobular carcinomas. The combination of both pesticides and either eserine or estrogen induced tumors with both types of structures followed by mammary gland tumors and metastasis to the lung and kidneys after 240 days of a 5-day treatment. Studies also showed that these pesticides and eserine decreased three to five times the acetylcholinesterase activity in the serum compared to controls whereas terminal end buds increased in number, being inhibited by atropine. Genomic instability was analyzed in such tissues (mp53, CYP1A2, c-myc, c-fos, ERα, M2R) and pesticides increased protein expression that was stimulated by estrogens but inhibited by atropine. Eserine also transformed the epithelium of the rat mammary gland in the presence of estrogen and increased the number of terminal end buds after treatment inducing mammary carcinomas. Then, enzymatic digestion of such structures gave rise to cells with increased DNA synthesis and induced anchorage independence. Thus, there were changes in the epithelium of the mammary gland influencing breast carcinogenesis. Furthermore, these substances and acetylcholine also showed the signs of carcinogenicity in vitro as cell proliferation, receptor expression (ERα, ErbB2, M2R), genomic instability (c-myc, mp53, ERα, M2R), and cell metabolism. A unique cellular model is also presented here based on the use of MCF-10 F, a non-tumorigenic cell line that represents a valuable clinically translatable experimental approach that identifies mechanistic links for pesticides and estrogen as suspect human carcinogenic agents.

The present study explored the effects of combination of Tinospora cordifolia and Arabinogalactan on surface membrane dynamics and programmed cell deaths in rat model of lung cancer. The rats were divided into different groups namely normal control, benzo(a)pyrene (BP) treated, BP + Tinospora cordifolia (TC)-treated, BP + Arabinogalactan (A)-treated and BP + TC + A-treated groups. Significant changes were observed in the membrane dynamics of rats treated with BP. The carcinogen treatment demonstrated a marked decrease in membrane microviscosity. Also, excimer/monomer ratio and fluidity parameters of BP treated rats showed significant rise. On the other hand, combination of Tinospora cordifolia and Arabinogalactan improvised surface membrane dynamics. Moreover, micronuclei formation along with protein expression of bcl-2 showed significant increase in the lungs of BP treated rats. The combined treatment of Tinospora cordifolia and Arabinogalactan moderated the micronuclei formation in BP treated rats. Also, the combined treatment regulated the protein expressions of bcl-2 in BP-treated rats. As a result, marked improvement was noticed in apoptosis of BP treated cells treated with combination treatment. This study concludes that the Tinospora cordifolia and Arabinogalactan in combination improve the surface membrane dynamics and apoptosis in BP-treated rats.

Environmental exposure can increase the production of reactive oxygen species and deplete cellular antioxidants in humans, resulting in oxidatively generated damage to DNA that is both a useful biomarker of oxidative stress and indicator of carcinogenic hazard. Methods of oxidatively damaged DNA analysis have been developed and used in public health research since the 1990s. Advanced techniques detect specific lesions, but they might not be applicable to complex matrixes (e.g., tissues), small sample volume, and large-scale studies. The most reliable methods are characterized by (1) detecting relevant DNA oxidation products (e.g., premutagenic lesions), (2) not harboring technical problems, (3) being applicable to complex biological mixtures, and (4) having the ability to process a large number of samples in a reasonable period of time. Most effort has been devoted to the measurements of 8-oxo-7,8-dihydro-2'-deoxyguanine (8-oxodG), which can be analyzed by chromatographic, enzymic, and antibody-based methods. Results from validation trials have shown that certain chromatographic and enzymic assays (namely the comet assay) are superior techniques. The enzyme-modified comet assay has been popular because it is technically simpler than chromatographic assays. It is widely used in public health studies on environmental exposures such as outdoor air pollution. Validated biomarker assays on oxidatively damaged DNA have been used to fill knowledge gaps between findings in prospective cohort studies and hazards from contemporary sources of air pollution exposures. Results from each of these research fields feed into public health research as approaches to conduct primary prevention of diseases caused by environmental or occupational agents.

The age-specific trend of cancer incidence rates, but not its magnitude, is well described employing the multistage theory of carcinogenesis by Armitage and Doll in combination with the senescence model of Pompei and Wilson. We derived empirical parameters of the multistage-senescence model from U.S. Surveillance, Epidemiology, and End Results (SEER) incidence data from 2000–2003 and 2010–2013 for The Cancer Genome Atlas (TCGA) cancer types. Under the assumption of a constant tumor-specific transition rate between stages, there is an extremely strong linear relationship (P < 0.0001) between the number of stages and the stage transition rate. The senescence tumor suppression factor for 20 non-reproductive cancers is remarkably consistent (0.0099±0.0005); however, five female reproductive cancers have significantly higher tumor suppression. The peak incidence rate for non-reproductive cancers occurs at a younger age for cancers with fewer stages and their carcinogenic stages are of longer duration. Driver gene mutations are shown to contribute on average only about a third of the carcinogenic stages of different tumor types. A tumor’s accumulated incidence, calculated using a two-variable (age, stage) model, is strongly associated with intrinsic cancer risk. During both early adulthood and senescence, the pace of tumor suppression appears to be synchronized across most cancer types, suggesting the presence of overlapping evolutionary processes.

Hydroxyanthraquinones from plants have been used as both medicinal active ingredients and adulterants in slimming food supplements. Although sensible doses of certain natural hydroxyanthraquinones for laxative effects are generally safe in the short term, chronic intake has been related to tumorigenic, carcinogenic, and genotoxic effects. However, an increasing number of researchers are reporting the antiproliferative properties of the same ingredients in cancer cells, pointing towards a potential nutraceutical value for cancer prevention. Previous studies have evaluated anthraquinones’ anti-proliferative activity against various tumour cell lines and bioavailability in Caco-2 cells. However, there are scarce data about both their cytotoxicity in the later cell line and long-term stability. Therefore, this study will check the purity of several ‘aged’ samples using mutually complementary analytical techniques such as HPTLC and NMR assays as well as evaluate the anti-proliferative activity of the purest of these samples using the Caco-2 cell line. The chromatographic and spectroscopic analyses confirmed the long-term stability of those compounds, and their cytotoxic activity resulted in chrysazin (15 µg/mL) &gt, catenarin (27.29 µg/mL) &gt, rhein (49.55 µg/mL) &gt, helminthosporin (52.91 µg/mL) &gt, aloe-emodin (55.34 µg/mL). Our succinct review of the cytotoxicity of these compounds afforded two results: that this is the first clear report for catenarin being active in colon cancer cells and that this class of compounds needs to be better studied to clearly evaluate their benefit/risk profile in regard to both new chemo preventative nutraceuticals and anticancer therapies.

PurposeThe study assessed the levels of organochlorine pesticides (OCPs) and their potential non-carcinogenic and carcinogenic health risks in four regularly consumed fruit vegetables.Design/methodology/approachThe OCPs’ residues were quantified using a gas chromatograph coupled with an electron capture detector (GC-ECD) and the dietary exposure of children, and adult consumers to the detected OCPs was evaluated using carcinogenic and systemic health risk estimations.FindingsAldrin, endrin, endrin aldehyde, a-endosulfan, β-endosulfan, endosulfan sulphate, heptachlor, heptachlor epoxide and dieldrin were detected in the four fruit vegetables. The predominant OCP residue in carrot, cucumber, tomatoes and watermelon was endosulfan sulphate with mean concentrations of 2.532 mg kg−1, 1.729 mg kg−1, 2.363 mg kg−1 and 1.154 mg kg−1, respectively. The residues levels in some of the fruit vegetables were higher than their respective maximum residue levels (MRLs) of 0.01–0.05 mg kg−1 set by the European Commission with concentrations above MRLs ranging between 25.5% and 100%. The systemic health risk estimations showed that the hazard index (HI) values for carrot (3.20), cucumber (9.25), tomatoes (50.21) and watermelon (16.76) were >1 for children consumers and the respective HI values of 2.87, 15.57 and 5.20 for adult consumers of cucumber, tomatoes and watermelon were >1 which implies potential systemic health risks. Four carcinogens (aldrin, dieldrin, heptachlor and heptachlor epoxide) had cancer risk index values greater than the acceptable risk of 1 in 1 million for both adult and children consumers.Originality/valueThe paper shows that despite the ban on the use of OCPs in Nigeria, they are still being used for agricultural production especially on some locally produced and regularly consumed fruit vegetables as reported in the present study. The non-existence of surveillance programmes on pesticide usage and the lack of proper monitoring of pesticide residues in food products including fruit and vegetables must have contributed to the levels of the detected OCP in the samples analysed. The current daily intake of OCP via contaminated vegetables may pose potential health risks to both the children and adult consumers of the fruit vegetables.

Poly-m-chloroaniline has been synthesized by chemical oxidative polymerization of m-chloroaniline and confirmed by spectroscopic studies. Powder X-ray diffraction and FESEM studies confirmed ordered arrangement in poly-m-chloroaniline. The peak at lower angle such as 7.09° having d spacing of 12.53 Å shows ordered structure of PmClA which was further confirmed by layered morphology in the FESEM images. FTIR spectra confirm the stretching and vibration mode of polymeric m-chloroaniline ring. BET surface area and pore diameter of PmClA were found to be 121 m2/g and 15.184 nm. Poly-m-chloroaniline was found to have better adsorption capacity toward anionic dyes over cationic dyes. The anionic dye (IC and EY) was 98 and 99% removed in just 25 min, whereas the cationic dye (MG and Rh6G) was 87 and 83% removed in 30 min. Langmuir adsorption isotherm model and pseudo second-order kinetic equation fitted the data best. Mechanism of adsorption has also been proposed. This is suggested that polymeric materials can be used for purification of water. The reduction of aromatic nitro compounds to amino compounds using organocatalyst has been done for the first time.

Benzo (a) pyrene content in plants and soils in anthropogenically polluted areas pollution was monitored. The influence of benzo (a) pyrene on conifers and deciduous plants was assessed. In forests with Scots pine (Pinus sylvestris L.) and silver birch (Betula pendula) trunks, the content of lignin, cellulose, and extractive low molecular weight polar substances was determined by the concentration of benzo (a) pyrene and tree species. In forest ecosystems, the background content of carcinogen (1–5 μg / kg) did not affect the content of lignin and cellulose, but stimulated the synthesis of extractive substances, especially in birch. For pine, there was a direct correlation between the concentration of benzo (a) pyrene in two -year-old needles and its peroxidase activity. An increase in the activity of oxidoreductases and their participation in the synthesis of phenolic, tannin and other organic (extractive) substances, depending on the concentration of benzo (a) pyrene, indicate its biostimulating properties. Various physiological and biochemical reactions in woody and herbaceous plants were analyzed depending on the concentration (dose) of benzo (a) pyrene in the composition of plants and in soils polluted by anthropogenic emissions. Opposite reactions of coniferous and leafy trees to benzo (a) pyrene were observed. On the basis of own and published data, the natural, intermediate transitional and technogenic ranges of benzo (a) pyrene concentrations have been identified; among which the effect on plants varies from stimulating to inhibitory.

Introduction Antineoplastic drugs are widely used in the treatment of cancer. However, some are known carcinogens and reproductive toxins, and incidental low-level exposure to workers is a health concern. CAREX Canada estimated that approximately 75,000 Canadians are exposed to antineoplastic drugs in workplace settings. While policies and guidelines on safe handling of antineoplastic drugs are available, evidence suggests that compliance is low. In this paper, we identify barriers and facilitators for safe handling of antineoplastic drugs in workplace settings. Methods We utilized a unique method to study public policy which involved compiling policy levers, developing a logic model, conducting a literature review, and contextualizing data through a deliberative process with stakeholders to explore in-depth contextual factors and experiences for the safe handling of antineoplastic drugs. Results The most common barriers identified in the literature were: poor training (46%), poor safety culture (41%), and inconsistent policies (36%). The most common facilitators were: adequate safety training (41%), leadership support (23%), and consistent policies (21%). Several of these factors are intertwined and while this means one barrier can cause other barriers, it also allows healthcare employers to mitigate these barriers by implementing small but meaningful changes in the workplace. Conclusion The combination of barriers and facilitators identified in our review highlight the importance of creating work environments where safety is a priority for the safe handling of antineoplastic drugs. The results of this study will assist policy makers and managers in identifying gaps and enhancing strategies that reduce occupational exposure to antineoplastic drugs.

Human papillomavirus type 18 (HPV18) has high carcinogenic power in invasive cervical cancer (ICC) development. However, the underlying mechanism remains elusive. The carcinogenic properties of HPV18 require the PDZ‐binding motif of its E6 oncoprotein (HPV18 E6) to degrade its target PSD95/Dlg/ZO‐1 (PDZ) proteins. In this study, we demonstrated that the PDZ protein membrane‐associated guanylate kinase, WW and PDZ domain containing 3 (MAGI3) inhibited the Wnt/β‐catenin pathway, and subsequently cervical cancer (CC) cell migration and invasion, via decreasing β‐catenin levels. By reducing MAGI3 protein levels, HPV18 E6 promoted CC cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 was preferentially associated with the downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in CC. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in CC progression., By reducing the level of MAGI3 protein, HPV18 E6 promotes cervical cancer cell migration and invasion through activation of Wnt/β‐catenin signaling. Furthermore, HPV18 rather than HPV16 is preferentially associated with downregulation of MAGI3 and activation of the Wnt/β‐catenin pathway in cervical cancer. These findings shed light on the mechanism that gives HPV18 its high carcinogenic potential in cervical cancer progression.

Biomarkers of exposure to harmful tobacco constituents are key tools for identifying individuals at risk and developing interventions and tobacco control measures. However, tobacco biomarker studies are scarce in many parts of the world with high prevalence of tobacco use. Our goal was to establish a robust method for simultaneous analysis of urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N′-nitrosonornicotine (NNN), and cotinine at the Advanced Centre for Treatment, Research and Education in Cancer (ACTREC) in Mumbai, India. These biomarkers are validated measures of exposure to the carcinogenic tobacco nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and NNN and the addictive alkaloid nicotine, respectively. The established method is characterized by excellent accuracy, linearity, and precision, and was successfully applied to the analysis of 15 smokeless tobacco (SLT) users and 15 non-users of tobacco recruited in Mumbai. This is the first report of establishment of such procedure in a laboratory in India, which offers the first in-country capacity for research on tobacco carcinogenesis in Indian SLT users.

Increasing evidence highlights that microRNAs (miRNAs) drive glioma initiation and development. Nevertheless, the underlying role of miR-21-5p in glioma is elusive. Hence, we evaluated the underlying role of miR-21-5p in glioma progression. Microarray data analysis provided data indicating that the miR-21-5p level was elevated in glioma. Silenced miR-21-5p suppressed glioma cell growth and invasion. Additionally, our results disclosed that ten-eleven translocation 1 (TET1) was directly targeted by miR-21-5p. Furthermore, antagomir-21-5p restrained glioma cell growth in a xenograft tumour model. In rescue experiments, knockdown of TET1 neutralized miR-21-5p silence-mediated inhibitory function on glioma cell aggressiveness. Taken together, miR-21-5p exerted its carcinogenic effect in glioma cell growth and invasin by targeting TET1.

Most cases of mesothelioma are known to result from exposure to asbestos fibers in the environment or occupational ambient air. The following questions regarding asbestos toxicity remain partially unanswered: (i) why asbestos entering the alveoli during respiration exerts toxicity in the pleura; and (ii) how asbestos causes mesothelioma, even though human mesothelial cells are easily killed upon exposure to asbestos. As for the latter question, it is now thought that the frustrated phagocytosis of asbestos fibers by macrophages prolongs inflammatory responses and gives rise to a “mutagenic microenvironment” around mesothelial cells, resulting in their malignant transformation. Based on epidemiological and genetic studies, a carcinogenic model has been proposed in which BRCA1-associated protein 1 mutations are able to suppress cell death in mesothelial cells and increase genomic instability in the mutagenic microenvironment. This leads to additional mutations, such as CDKN2A [p16], NF2, TP53, LATS2, and SETD2, which are associated with mesothelioma carcinogenesis. Regarding the former question, the receptors involved in the intracellular uptake of asbestos and the mechanism of transfer of inhaled asbestos from the alveoli to the pleura are yet to be elucidated. Further studies using live-cell imaging techniques will be critical to fully understanding the mechanisms underlying asbestos toxicity.